Project Summary Ventricular tachycardia (VT) is an important cause of mortality and morbidity in patients with heart diseases. The majority of life-threatening VT episodes are caused by an electrical short circuit, formed by a narrow channel of surviving tissue inside myocardial scar. An important treatment for scar-related VT is to target and destroy these culprit slow-conducting channels. Effective ablation requires the ability to delineate the morphology of the circuit in order to identify the slow-conducting channels. Unfortunately, with conventional catheter mapping, up to 90% of the VT circuits are too short-lived to be mapped. For the 10% ?mappable? VTs, their data are available only during ablation and limited to one ventricular surface. This inadequacy of functional VT data largely limits our current knowledge about scar-related VT and ablation strategies, and reduces the ability of clinicians to identify ablation targets and assess ablation outcome. The goal of this proposal is to develop a novel technique to provide pre- and post-ablation functional VT data ? integrated with LGE-MRI scar data in 3D ? to improve VT ablation with pre-procedural identification of ablation targets and post-procedural mechanistic elucidation of ablation failure. It builds on the rapidly increasing clinical interest in electrocardiographic imaging (ECGi), an emerging technique that obtains cardiac electrical activity through inverse reconstructions from body-surface ECGs. Its specific objectives include: 1) To develop and validate a peri-procedural ECGi for mapping scar-related VT circuits. 2) To integrate LGE-MRI scar into ECGi for improved electroanatomical investigations of VT circuits. 3) To perform clinical evaluation of pre-ablation and post-ablation MRI-ECGi of scar-related VT. These investigations will be carried out on a prospective cohort of 40 patients with VT due to previous infarction. This research builds on our previously established technical foundation for transmural ECGi and promising preliminary data generated under the support of our exploratory NIH grant. It is further supported by previous technical and clinical advances in each of the subcontractors' lab, including camera-based torso modeling (Siemens), intramural mapping and ablation (NSHA), and LGE-MRI scar imaging in VT (UPenn). The outcome of this research will generate new knowledge about the electroanatomical mechanism of scar-related VT and the mechanism behind ablation failure. It will enable pre- and post-procedural mapping of 3D functional circuits of all inducible VTs, improving the ability of clinicians to identify ablation targets and assess ablation outcome. Finally, it will timely deliver the next generation of ECGi techniques to further our general technical capability for safer and more efficient cardiac electrophysiological studies in a broader variety of heart diseases.